TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21135	63628;63629;63630	chr2:178588004;178588003;178588002	chr2:179452731;179452730;179452729
N2AB	19494	58705;58706;58707	chr2:178588004;178588003;178588002	chr2:179452731;179452730;179452729
N2A	18567	55924;55925;55926	chr2:178588004;178588003;178588002	chr2:179452731;179452730;179452729
N2B	12070	36433;36434;36435	chr2:178588004;178588003;178588002	chr2:179452731;179452730;179452729
Novex-1	12195	36808;36809;36810	chr2:178588004;178588003;178588002	chr2:179452731;179452730;179452729
Novex-2	12262	37009;37010;37011	chr2:178588004;178588003;178588002	chr2:179452731;179452730;179452729
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-41
• Domain position: 72
• Structural Position: 97
• Q(SASA): 0.0889
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
L/V	rs1218574817	-2.054	0.999	D	0.843	0.659	0.699352526576	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
L/V	rs1218574817	-2.054	0.999	D	0.843	0.659	0.699352526576	gnomAD-4.0.0	4.78037E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86133E-06	1.43365E-05	3.02847E-05

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
L/A	0.8712	likely_pathogenic	0.8978	pathogenic	-2.635	Highly Destabilizing	0.999	D	0.782	deleterious	None	None	None	None	N
L/C	0.88	likely_pathogenic	0.9084	pathogenic	-2.142	Highly Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
L/D	0.9976	likely_pathogenic	0.9983	pathogenic	-2.772	Highly Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
L/E	0.9866	likely_pathogenic	0.9889	pathogenic	-2.578	Highly Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
L/F	0.762	likely_pathogenic	0.782	pathogenic	-1.765	Destabilizing	1.0	D	0.828	deleterious	D	0.63943813	None	None	N
L/G	0.9766	likely_pathogenic	0.981	pathogenic	-3.168	Highly Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
L/H	0.9761	likely_pathogenic	0.9813	pathogenic	-2.549	Highly Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
L/I	0.2577	likely_benign	0.2942	benign	-1.106	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
L/K	0.973	likely_pathogenic	0.9776	pathogenic	-1.95	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
L/M	0.3686	ambiguous	0.3872	ambiguous	-1.07	Destabilizing	1.0	D	0.8	deleterious	D	0.595326846	None	None	N
L/N	0.9879	likely_pathogenic	0.9905	pathogenic	-2.232	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
L/P	0.9639	likely_pathogenic	0.9712	pathogenic	-1.595	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/Q	0.9543	likely_pathogenic	0.9607	pathogenic	-2.159	Highly Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
L/R	0.9429	likely_pathogenic	0.9522	pathogenic	-1.584	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
L/S	0.979	likely_pathogenic	0.9841	pathogenic	-2.99	Highly Destabilizing	1.0	D	0.781	deleterious	D	0.665783459	None	None	N
L/T	0.8727	likely_pathogenic	0.896	pathogenic	-2.643	Highly Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
L/V	0.2949	likely_benign	0.3369	benign	-1.595	Destabilizing	0.999	D	0.843	deleterious	D	0.588160102	None	None	N
L/W	0.9528	likely_pathogenic	0.9628	pathogenic	-2.078	Highly Destabilizing	1.0	D	0.681	prob.neutral	D	0.665783459	None	None	N
L/Y	0.9753	likely_pathogenic	0.9801	pathogenic	-1.812	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.